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1.
Nano Lett ; 24(7): 2242-2249, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38346395

RESUMO

Bioorthogonal catalysis employing transition metal catalysts is a promising strategy for the in situ synthesis of imaging and therapeutic agents in biological environments. The transition metal Pd has been widely used as a bioorthogonal catalyst, but bare Pd poses challenges in water solubility and catalyst stability in cellular environments. In this work, Pd(0) loaded amphiphilic polymeric nanoparticles are applied to shield Pd in the presence of living cells for the in situ generation of a fluorescent dye and anticancer drugs. Pd(0) loaded polymeric nanoparticles prepared by the reduction of the corresponding Pd(II)-polymeric nanoparticles are highly active in the deprotection of pro-rhodamine dye and anticancer prodrugs, giving significant fluorescence enhancement and toxigenic effects, respectively, in HepG2 cells. In addition, we show that the microstructure of the polymeric nanoparticles for scaffolding Pd plays a critical role in tuning the catalytic efficiency, with the use of the ligand triphenylphosphine as a key factor for improving the catalyst stability in biological environments.


Assuntos
Antineoplásicos , Nanopartículas , Pró-Fármacos , Humanos , Pró-Fármacos/química , Antineoplásicos/química , Nanopartículas/química , Polímeros/química , Células Hep G2 , Catálise
2.
Small ; 20(6): e2305169, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37797194

RESUMO

Bacterial infections are a public health threat of increasing concern in medical care systems; hence, the search for novel strategies to lower the use of antibiotics and their harmful effects becomes imperative. Herein, the antimicrobial performance of four polyoxometalate (POM)-stabilized gold nanoparticles (Au@POM) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as Gram-negative and Gram-positive bacteria models, respectively, is studied. The bactericidal studies performed, both in planktonic and sessile forms, evidence the antimicrobial potential of these hybrid nanostructures with selectivity toward Gram-negative species. In particular, the Au@GeMoTi composite with the novel [Ti2 (HGeMo7 O28 )2 ]10- POM capping ligand exhibits outstanding bactericidal efficiency with a minimum inhibitory concentration of just 3.12 µm for the E. coli strain, thus outperforming the other three Au@POM counterparts. GeMoTi represents the fourth example of a water-soluble TiIV -containing polyoxomolybdate, and among them, the first sandwich-type structure having heteroatoms in high-oxidation state. The evaluation of the bactericidal mechanisms of action points to the cell membrane hyperpolarization, disruption, and subsequent nucleotide leakage and the low cytotoxicity exerted on five different cell lines at antimicrobial doses demonstrates the antibiotic-like character. These studies highlight the successful design and development of a new POM-based nanomaterial able to eradicate Gram-negative bacteria without damaging mammalian cells.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Infecções Estafilocócicas , Animais , Ouro/química , Escherichia coli , Titânio/farmacologia , Staphylococcus aureus , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Mamíferos
3.
Br J Neurosurg ; : 1-5, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836514

RESUMO

Pilocytic Astrocytomas are generally presenting as WHO grade 1 intracranial masses in the paediatric population with a favourable prognostic. In less common instances they can be found in the spinal cord. There have been rare cases of Anaplastic variants of the Cranial Pilocytic Astrocytomas. We report a rare instance of an adult patient with pilocytic astrocytoma of the cervical cord with anaplastic features. Our patient presented with 6 months history of neck pain and right-hand paraesthesia which partially responded to steroid treatment. MRI of the cervical spine demonstrated marked expansion of the cervical cord with oedema extending cranially to the medulla and caudally to the mid-thoracic cord. Post-gadolinium T1-weighted images showed intense intramedullary enhancement mainly centred at the level of the C3 vertebra. Diffusion Tensor Imaging Tractography showed the central location of the tumour expanding the cord and displacing the tracts circumferentially. Surgical resection was performed in two stages according to the Elsberg and Beer technique that assisted with safe margin tumour debulking. The histological sections revealed a glial lineage tumour with retained ATRX nuclear expression, positive for GFAP, Ki-67 estimated to 10% and a methylation class corresponding to an Anaplastic Pilocytic Astrocytoma. Subsequently, our patient underwent adjuvant radiotherapy and chemotherapy (10 cycles of Temozolamide and 6 cycles of CCNU). Symptomatic progression developed at 18 months from the initial surgery, radiological progression at 34 months and the overall survival was 40 months. We reviewed the literature and found only four other cases with similar histology.

4.
Nano Lett ; 23(3): 804-811, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36648322

RESUMO

Bioorthogonal metallocatalysis has opened up a xenobiotic route to perform nonenzymatic catalytic transformations in living settings. Despite their promising features, most metals are deactivated inside cells by a myriad of reactive biomolecules, including biogenic thiols, thereby limiting the catalytic functioning of these abiotic reagents. Here we report the development of cytocompatible alloyed AuPd nanoparticles with the capacity to elicit bioorthogonal depropargylations with high efficiency in biological media. We also show that the intracellular catalytic performance of these nanoalloys is significantly enhanced by protecting them following two different encapsulation methods. Encapsulation in mesoporous silica nanorods resulted in augmented catalyst reactivity, whereas the use of a biodegradable PLGA matrix increased nanoalloy delivery across the cell membrane. The functional potential of encapsulated AuPd was demonstrated by releasing the potent chemotherapy drug paclitaxel inside cancer cells. Nanoalloy encapsulation provides a novel methodology to develop nanoreactors capable of mediating new-to-life reactions in cells.


Assuntos
Nanotubos , Paládio , Ligas , Paclitaxel , Catálise
5.
Inorg Chem ; 61(48): 19261-19273, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36383699

RESUMO

Novel heteronuclear IrIII-CuII coordination compounds ([Ir(η5-Cp*)Cl2Pcfx-Cu(phen)](NO3)·1.75(CH3OH)·0.75(H2O) (1), [Ir(η5-Cp*)Cl2Pnfx-Cu(phen)](NO3)·1.75(CH3OH)·0.75(H2O) (2), [Ir(η5-Cp*)Cl2Plfx-Cu(phen)](NO3)·1.3(H2O)·1.95(CH3OH) (3), [Ir(η5-Cp*)Cl2Psfx-Cu(phen)] (4)) bearing phosphines derived from fluoroquinolones, namely, sparfloxacin (Hsfx), ciprofloxacin (Hcfx), lomefloxacin (Hlfx), and norfloxacin (Hnfx), have been synthesized and studied as possible anticancer chemotherapeutics. All compounds have been characterized by electrospray ionization mass spectrometry (ESI-MS), a number of spectroscopic methods (i.e., IR, fluorescence, and electron paramagnetic resonance (EPR)), cyclic voltammetry, variable-temperature magnetic susceptibility measurements, and X-ray diffractometry. The coordination geometry of IrIII in all complexes adopts a characteristic piano-stool geometry with the η5-coordinated and three additional sites occupied by two chloride and phosphine ligands, while CuII ions in complexes 1 and 2 form a distorted square-pyramidal coordination geometry, and in complex 3, the coordination geometry around CuII ions is a distorted octahedron. Interestingly, the crystal structure of [Ir(η5-Cp*)Cl2Plfx-Cu(phen)] features the one-dimensional (1D) metal-organic polymer. Liposomes loaded with redox-active and fluorescent [Ir(η5-Cp*)Cl2Pcfx-Cu(phen)] (1L) have been prepared to increase water solubility and minimize serious systemic side effects. It has been proven, by confocal microscopy and an inductively coupled plasma mass spectrometry (ICP-MS) analysis, that the liposomal form of compound 1 can be effectively accumulated inside human lung adenocarcinoma and human prostate carcinoma cells with selective localization in nuclei. A cytometric analysis showed dominance of apoptosis over the other cell death types. Furthermore, the investigated nanoformulations induced changes in the cell cycle, leading to S phase arrest in a dose-dependent manner. Importantly, in vitro anticancer action on three-dimensional (3D) multicellular tumor spheroids has been demonstrated.


Assuntos
Carcinoma , Complexos de Coordenação , Humanos , Masculino , Cobre/química , Lipossomos , Próstata , Íons , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Cristalografia por Raios X
6.
J Nanobiotechnology ; 20(1): 473, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335359

RESUMO

BACKGROUND: Platinum nanoparticles have been demonstrated to have excellent anticancer properties. However, because of the lack of specificity they must be delivered to the tumor in amounts sufficient to reach the desired therapeutic objectives. Interestingly, exosomes are considered as excellent natural selective delivery nanotools, but until know their targeting properties have not being combined with the anticancer properties of platinum nanoparticles. RESULTS: In this work we combine the targeting capabilities of exosomes and the antitumoral properties of ultrasmall (< 2 nm) platinum nanoparticles as a novel, low toxicity alternative to the use of cisplatin. A mild methodology based on the room temperature CO-assisted in situ reduction of Pt2+ precursor was employed to preserve the integrity of exosomes, while generating ultrasmall therapeutic PtNPs directly inside the vesicles. The resulting PtNPs-loaded exosomes constitute a novel hybrid bioartificial system that was readily internalized by the target cells inducing antiproliferative response, as shown by flow cytometry and microscopy experiments in vitro. In vivo Pt-Exos showed antitumoral properties similar to that of cisplatin but with a strongly reduced or in some cases no toxic effect, highlighting the advantages of this approach and its potential for translation to the clinic. CONCLUSIONS: In this study, a nanoscale vector based on ultrasmall PtNPs and exosomes has been created exhibiting antitumoral properties comparable or higher to those of the FDA approved cisplatin. The preferential uptake of PtNPs mediated by exosomal transfer between certain cell types has been exploited to create a selective antitumoral novel bioartificial system. We have demonstrated their anticancer properties both in vitro and in vivo comparing the results obtained with the administration of equivalent amounts of cisplatin, and showing a spectacular reduction of toxicity.


Assuntos
Exossomos , Nanopartículas Metálicas , Nanopartículas , Neoplasias , Humanos , Cisplatino/farmacologia , Platina , Linhagem Celular Tumoral
7.
Artif Organs ; 46(3): 412-426, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34606117

RESUMO

BACKGROUND: Membranes based on triply periodic minimal surfaces (TPMS) have proven a superior gas transfer compared to the contemporary hollow fiber membrane (HFM) design in artificial lungs. The improved oxygen transfer is attributed to disrupting the laminar boundary layer adjacent to the membrane surface known as main limiting factor to mass transport. However, it requires experimental proof that this improvement is not at the expense of greater damage to the blood. Hence, the aim of this work is a valid statement regarding the structure-dependent hemolytic behavior of TPMS structures compared to the current HFM design. METHODS: Hemolysis tests were performed on structure samples of three different kind of TPMS-based designs (Schwarz-P, Schwarz-D and Schoen's Gyroid) in direct comparison to a hollow fiber structure as reference. RESULTS: The results of this study suggest that the difference in hemolysis between TPMS membranes compared to HFMs is small although slightly increased for the TPMS membranes. There is no significant difference between the TPMS structures and the hollow fiber design. Nevertheless, the ratio between the achieved additional oxygen transfer and the additional hemolysis favors the TPMS-based membrane shapes. CONCLUSION: TPMS-shaped membranes offer a safe way to improve gas transfer in artificial lungs.


Assuntos
Órgãos Artificiais , Hemólise , Pulmão , Membranas Artificiais , Desenho de Equipamento , Humanos , Impressão Tridimensional
8.
Artif Organs ; 46(1): 71-82, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34287976

RESUMO

The objective of this study is to identify the preload and afterload sensitivity of the ReinHeart TAH 2.0. For adequate left-right flow balance, the concept of a reduced right stroke volume (by about 10%) and active adaption of the right diastole duration are evaluated concerning the controllability of the flow balance. This study used an active mock circulation loop to test a wide range of preload and afterload conditions. Preload sensitivity was tested at atrial pressures (APs) between 4 and 20 mm Hg. Left afterload was varied in a range of 60-140 mm Hg mean aortic pressure (MAP), right afterload was simulated between 15 and 40 mm Hg. Four scenarios were developed to verify that the flow difference fully covers the defined target range of 0-1.5 L/min. Although a positive correlation between inlet pressure and flow is identified for the right pump chamber, the left pump chamber already fills completely at an inlet pressure of 8-10 mm Hg. With increasing afterload, both the left and right flow decrease. A positive flow balance (left flow exceeds right flow) is achieved over the full range of tested afterloads. At high APs, the flow difference is limited to a maximum of 0.7 L/min. The controllability of flow balance was successfully evaluated in four scenarios, revealing that a positive flow difference can be achieved over the full range of MAPs. Under physiological test conditions, the linear relationship between flow and heart rate was confirmed, ensuring good controllability of the TAH.


Assuntos
Circulação Sanguínea , Coração Artificial , Desenho de Prótese , Pressão Sanguínea , Frequência Cardíaca , Hidrodinâmica , Modelos Cardiovasculares
9.
J Artif Organs ; 25(1): 1-8, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33956261

RESUMO

An in-vitro study was conducted to investigate the general feasibility of using only one pumping chamber of the SynCardia total artificial heart (TAH) as a replacement of the single ventricle palliated by Fontan circulation. A mock circulation loop was used to mimic a Fontan circulation. The combination of both ventricle sizes (50 and 70 cc) and driver (Freedom Driver and Companion C2 Driver) was investigated. Two clinical relevant scenarios (early Fontan; late Fontan) as derived from literature data were set up in the mock loop. The impact of increased transpulmonary pressure gradient, low atrial pressure, and raised central venous pressure on cardiac output was studied. From a hemodynamic point, the single-chambered TAH performed sufficiently in the setting of the Fontan circulation. Increased transpulmonary pressure gradient, from ideal to pulmonary hypertension, decreased the blood flow in combinations by almost 2 L/min. In the early Fontan scenario, a cardiac output of 3-3.5 L/min was achieved using the 50 cc ventricle, driven by the Companion C2 Driver. Even under pulmonary hypertension, cardiac outputs greater than 4 L/min could be obtained with the 70 cc pump chamber in the late Fontan scenario. In the clinically relevant Fontan scenarios, implementation of the single chambered TAH performed successfully from a hemodynamic point of view. The replacement of the failing univentricular heart by a single chamber of the SynCardia TAH may provide an alternative to a complex biventricular repair procedure or ventricular support in Fontan patients.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Coração Artificial , Débito Cardíaco , Técnica de Fontan/métodos , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/cirurgia , Hemodinâmica/fisiologia , Humanos
10.
Int J Mol Sci ; 23(23)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36499657

RESUMO

Hematological and hemorheological parameters are known to be altered in COVID-19; however, the value of combined monitoring in order to deduce disease severity is only scarcely examined. A total of 44 acute SARS-CoV-2-infected patients (aCOV) and 44 age-matched healthy controls (Con) were included. Blood of aCOV was sampled at admission (T0), and at day 2 (T2), day 5 (T5), day 10 (T10), and day 30 (T30) while blood of Con was only sampled once. Inter- and intra-group differences were calculated for hematological and hemorheological parameters. Except for mean cellular volume and mean cellular hemoglobin, all blood cell parameters were significantly different between aCOV and Con. During the acute disease state (T0-T5), hematological and hemorheological parameters were highly altered in aCOV; in particular, anemic conditions and increased immune cell response/inflammation, oxidative/nitrosative stress, decreased deformability, as well as increased aggregation, were observed. During treatment and convalescence until T30, almost all abnormal values of aCOV improved towards Con values. During the acute state of the COVID-19 disease, the hematological, as well as the hemorheological system, show fast and potentially pathological changes that might contribute to the progression of the disease, but changes appear to be largely reversible after four weeks. Measuring RBC deformability and aggregation, as well as oxidative stress induction, may be helpful in monitoring critically ill COVID-19 patients.


Assuntos
COVID-19 , Hematologia , Humanos , Hemorreologia , SARS-CoV-2 , Índices de Eritrócitos , Estado Terminal , Agregação Eritrocítica
11.
Chemistry ; 27(9): 2993-2996, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33231902

RESUMO

The combination of 2D materials opens a wide range of possibilities to create new-generation structures with multiple applications. Covalently cross-linked approaches are a ground-breaking strategy for the formation of homo or heterostructures made by design. However, the covalent assembly of transition metal dichalcogenides flakes is relatively underexplored. Here, a simple covalent cross-linking method to build 2H-MoS2 -MoS2 homostructures is described, using commercially available bismaleimides. These assemblies are mainly connected vertically, basal plane to basal plane, creating specific molecular sized spaces between MoS2 sheets. Therefore, this straightforward approach gives access to the controlled connection of sulfide-based 2D materials.

12.
Bioorg Med Chem ; 41: 116217, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34022529

RESUMO

The recent incorporation of Au chemistry in the bioorthogonal toolbox has opened up new opportunities to deliver biologically independent reactions in living environments. Herein we report that the O-propargylation of the hydroxamate group of the potent HDAC inhibitor panobinostat leads to a vast reduction of its anticancer properties (>500-fold). We also show that this novel prodrug is converted back into panobinostat in the presence of Au catalysts in vitro and in cell culture.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Panobinostat/química , Panobinostat/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular , Ouro , Humanos
13.
Artif Organs ; 45(1): 68-78, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32750157

RESUMO

Transcatheter aortic valve replacement (TAVR) has emerged as a widely used therapy for aortic valve diseases. With TAVR, flow hemodynamics may change leading to areas of flow stagnation prone to thrombosis risk. The neo-sinus, created by introducing a prosthesis inside the diseased native valve, may prompt leaflet thrombosis due to areas of flow stasis. This study attempted to understand the effect of different prosthesis implant depths on the flow field within the neo- and native sinus and on the coronary perfusion. Experiments were performed inside an in vitro pulse duplicator producing physiological conditions according to ISO 5840-1:2015 standard. Flow fields were obtained for two cardiac outputs (CO) using particle image velocimetry (PIV). Washout was calculated as a measure of flow stasis. The two main results are: a lower implant position and a lower CO/frequency led to better native sinus washout, but worsened neo-sinus washout. In contrast, a higher implant position led to higher coronary flow (for higher CO/frequency). No significant effect of implant depth on coronary flow was observed for lower CO/frequency. In summary, a higher implant position using this self-expanding prosthesis is associated with reduced neo-sinus flow stasis. Hereby, washout of the native sinus, as well as coronary flow, are dependent on cardiac output.


Assuntos
Estenose da Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Modelos Cardiovasculares , Desenho de Prótese , Substituição da Valva Aórtica Transcateter/efeitos adversos , Valva Aórtica/fisiopatologia , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/fisiopatologia , Velocidade do Fluxo Sanguíneo , Débito Cardíaco , Circulação Coronária , Humanos , Reologia , Substituição da Valva Aórtica Transcateter/métodos , Resultado do Tratamento
14.
Hepatology ; 70(1): 108-126, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30706949

RESUMO

Gene therapy with an adeno-associated vector (AAV) serotype 8 encoding the human ATPase copper-transporting beta polypeptide (ATP7B) complementary DNA (cDNA; AAV8-ATP7B) is able to provide long-term copper metabolism correction in 6-week-old male Wilson disease (WD) mice. However, the size of the genome (5.2 kilobases [kb]) surpasses the optimal packaging capacity of the vector, which resulted in low-yield production; in addition, further analyses in WD female mice and in animals with a more advanced disease revealed reduced therapeutic efficacy, as compared to younger males. To improve efficacy of the treatment, an optimized shorter AAV vector was generated, in which four out of six metal-binding domains (MBDs) were deleted from the ATP7B coding sequence, giving rise to the miniATP7B protein (Δ57-486-ATP7B). In contrast to AAV8-ATP7B, AAV8-miniATP7B could be produced at high titers and was able to restore copper homeostasis in 6- and 12-week-old male and female WD mice. In addition, a recently developed synthetic AAV vector, AAVAnc80, carrying the miniATP7B gene was similarly effective at preventing liver damage, restoring copper homeostasis, and improving survival 1 year after treatment. Transduction of approximately 20% of hepatocytes was sufficient to normalize copper homeostasis, suggesting that corrected hepatocytes are acting as a sink to eliminate excess of copper. Importantly, administration of AAVAnc80-miniATP7B was safe in healthy mice and did not result in copper deficiency. Conclusion: In summary, gene therapy using an optimized therapeutic cassette in different AAV systems provides long-term correction of copper metabolism regardless of sex or stage of disease in a clinically relevant WD mouse model. These results pave the way for the implementation of gene therapy in WD patients.


Assuntos
ATPases Transportadoras de Cobre/genética , Cobre/metabolismo , Terapia Genética/métodos , Degeneração Hepatolenticular/terapia , Animais , ATPases Transportadoras de Cobre/metabolismo , Dependovirus , Modelos Animais de Doenças , Feminino , Vetores Genéticos , Degeneração Hepatolenticular/mortalidade , Homeostase , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL
15.
Chemistry ; 26(29): 6629-6634, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32101348

RESUMO

Most air-stable 2D materials are relatively inert, which makes their chemical modification difficult. In particular, in the case of MoS2 , the semiconducting 2 H-MoS2 is much less reactive than its metallic counterpart, 1T-MoS2 . As a consequence, there are hardly any reliable methods for the covalent modification of 2 H-MoS2 . An ideal method for the chemical functionalization of such materials should be both mild, not requiring the introduction of a large number of defects, and versatile, allowing for the decoration with as many different functional groups as possible. Herein, a comprehensive study on the covalent functionalization of 2 H-MoS2 with maleimides is presented. The use of a base (Et3 N) leads to the in situ formation of a succinimide polymer layer, covalently connected to MoS2 . In contrast, in the absence of base, functionalization stops at the molecular level. Moreover, the functionalization protocol is mild (occurs at room temperature), fast (nearly complete in 1 h), and very flexible (11 different solvents and 10 different maleimides tested). In practical terms, the procedures described here allow for the chemist to manipulate 2 H-MoS2 in a very flexible way, decorating it with polymers or molecules, and with a wide range of functional groups for subsequent modification. Conceptually, the spurious formation of an organic polymer might be general to other methods of functionalization of 2D materials, where a large excess of molecular reagents is typically used.

16.
Mol Pharm ; 17(9): 3314-3327, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32687366

RESUMO

Copolymers synthesized from acrylic acid and methacrylic acid used as gastroprotective and mucoadhesive enteric coatings have been used to prepare micro- (∼2 µm), submicro- (∼200 nm), and nanoparticles (∼20 nm) containing rifampicin (Rif) to obtain time-controlled drug release kinetics. Different particle sizes and drug release kinetics have been obtained using different synthesis conditions and fabrication techniques including the use of an electrosprayer and an interdigital microfabricated micromixer. The antimicrobial action of the encapsulated Rif has been demonstrated against Staphylococcus aureus ATCC 25923 and compared with the effect of the equivalent dose of the free macrolide antibiotic. At low concentrations, the encapsulated antibiotic showed superior antimicrobial activity than the free drug. The stability of the developed particles has been evaluated in vitro under simulated gastric and intestinal conditions. At the concentrations tested, a reduced cytotoxicity against different human cell lines was observed after analyzing their subcytotoxic doses and the influence on their cell cycle by flow cytometry. Drug release kinetics can be tuned by adjusting particle sizes, and it would be possible to reach the minimum inhibitory concentration or the minimum bactericidal concentration at different time points depending on the medical needs.


Assuntos
Antibacterianos/química , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Polímeros/química , Administração Oral , Antibacterianos/farmacologia , Células CACO-2 , Linhagem Celular Tumoral , Preparações de Ação Retardada/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Humanos , Concentração de Íons de Hidrogênio , Cinética , Metacrilatos/química , Testes de Sensibilidade Microbiana/métodos , Nanopartículas/química , Tamanho da Partícula , Ácidos Polimetacrílicos/química , Rifampina/química , Rifampina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos
17.
J Nanobiotechnology ; 18(1): 150, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092584

RESUMO

BACKGROUND: Exosomes are endocytic-extracellular vesicles with a diameter around 100 nm that play an essential role on the communication between cells. In fact, they have been proposed as candidates for the diagnosis and the monitoring of different pathologies (such as Parkinson, Alzheimer, diabetes, cardiac damage, infection diseases or cancer). RESULTS: In this study, magnetic nanoparticles (Fe3O4NPs) were successfully functionalized with an exosome-binding antibody (anti-CD9) to mediate the magnetic capture in a microdevice. This was carried out under flow in a 1.6 mm (outer diameter) microchannel whose wall was in contact with a set of NdFeB permanent magnets, giving a high magnetic field across the channel diameter that allowed exosome separation with a high yield. To show the usefulness of the method, the direct capture of exosomes from whole blood of patients with pancreatic cancer (PC) was performed, as a proof of concept. The captured exosomes were then subjected to analysis of CA19-9, a protein often used to monitor PC patients. CONCLUSIONS: Here, we describe a new microfluidic device and the procedure for the isolation of exosomes from whole blood, without any need of previous isolation steps, thereby facilitating translation to the clinic. The results show that, for the cases analyzed, the evaluation of CA19-9 in exosomes was highly sensitive, compared to serum samples.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Antígenos Glicosídicos Associados a Tumores/isolamento & purificação , Análise Química do Sangue/métodos , Exossomos/química , Neoplasias Pancreáticas/diagnóstico , Anticorpos/química , Anticorpos/metabolismo , Boro/química , Campos Eletromagnéticos , Humanos , Ferro/química , Dispositivos Lab-On-A-Chip , Nanopartículas de Magnetita/química , Neodímio/química , Propriedades de Superfície
18.
BMC Cancer ; 19(1): 666, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277602

RESUMO

BACKGROUND: Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones. METHODS: We produced clonal cell lines derived from the MDA-MB-231 breast cancer cell line, using the UbC-StarTrack system, which allowed tracking of multiple clones by color: GFP C3, mKO E10 and Sapphire D7. Characterization of these clones was performed by growth rate, cell metabolic activity, wound healing, invasion assays and genetic and epigenetic arrays. Tumorigenicity was tested by orthotopic and intravenous injections. Clonal cooperation was evaluated by medium complementation, co-culture and co-injection assays. RESULTS: Characterization of these clones in vitro revealed clear genetic and epigenetic differences that affected growth rate, cell metabolic activity, morphology and cytokine expression among cell lines. In vivo, all clonal cell lines were able to form tumors; however, injection of an equal mix of the different clones led to tumors with very few mKO E10 cells. Additionally, the mKO E10 clonal cell line showed a significant inability to form lung metastases. These results confirm that even in stable cell lines heterogeneity is present. In vitro, the complementation of growth medium with medium or exosomes from parental or clonal cell lines increased the growth rate of the other clones. Complementation assays, co-growth and co-injection of mKO E10 and GFP C3 clonal cell lines increased the efficiency of invasion and migration. CONCLUSIONS: These findings support a model where interplay between clones confers aggressiveness, and which may allow identification of the factors involved in cellular communication that could play a role in clonal cooperation and thus represent new targets for preventing tumor progression.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Células Clonais/metabolismo , Heterogeneidade Genética , Animais , Apoptose , Comunicação Celular , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Células Clonais/patologia , Técnicas de Cocultura , Citocinas/análise , Elementos de DNA Transponíveis/genética , Feminino , Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Peixe-Zebra
19.
Langmuir ; 35(6): 2236-2243, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30642186

RESUMO

The synthesis of alloyed nanoparticles has been studied extensively; however, the formation mechanisms involved remain unclear. Here, we reveal the detailed formation mechanism of alloyed nanoparticles in a Pd-Ru system, using a semibatch polyol method in which the simultaneous rapid reduction of both precursors was assumed to be the critical mechanism. We employed a microflow reactor to realize rapid heating and cooling. A significant difference in the reaction rate between the two precursors was observed. Pd was reduced within seconds, but the reduction of Ru was 2 orders of magnitude slower than that of Pd and was not as rapid as previously assumed. Further investigation of the semibatch method was performed to trace changes in the particle sizes and composition. Through quantitative and multilateral evidence, we concluded that the formation of low-crystallinity seeds, followed by solid-state diffusion, is the governing mechanism for the formation of alloyed Pd-Ru nanoparticles.

20.
Analyst ; 144(2): 488-497, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30467573

RESUMO

The present work aims to study the effects that acute exposure to low concentrations of silver nanoparticles (AgNPs) cause in digestive glands of terrestrial isopods (Porcellio scaber). The experiments were designed to integrate different analytical techniques, such as transmission electron microscopy, atomic absorption spectroscopy, proton induced X-ray emission, and Fourier transform IR imaging (FTIRI), in order to gain a comprehensive insight into the process from the AgNPs' synthesis to their interaction with biological tissues in vivo. To this aim, terrestrial isopods were fed with AgNPs having different shapes, sizes, and concentrations. For all the tested conditions, no toxicity at the whole organism level was observed after 14 days of exposure. However, FTIRI showed that AgNPs caused detectable local changes in proteins, lipids, nucleic acids and carbohydrates at the tissue level, to an extent dependent on the interplay of the AgNPs' properties: shape, size, concentration and dissolution of ions from them.


Assuntos
Isópodes/química , Nanopartículas Metálicas/química , Prata/química , Animais , Feminino , Mucosa Intestinal/química , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Isópodes/efeitos dos fármacos , Isópodes/metabolismo , Masculino , Nanopartículas Metálicas/administração & dosagem , Microscopia , Tamanho da Partícula , Análise de Componente Principal , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
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